Cellular Origins of Endometriosis: Towards Novel Diagnostics and Therapeutics

Filby, Caitlin E.; Rombauts, Luk; Montgomery, Grant W.; Giudice, Linda C.; Gargett, Caroline E.

doi:10.1055/s-0040-1713429

Cited by 25 publications

(24 citation statements)

References 129 publications

(161 reference statements)

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“…Those epithelial and stromal progenitor cells in adenomyosis then develop independently from the adjacent endometrium basalis once they reside in the myometrium, similar to the development of peritoneal endometriosis, as proposed in a previous study [42]. In a recent report, Filby et al [43] found that the endometrial epithelial progenitors and perivascular mesenchymal stem cells residing in the basalis are highly clonogenic and have multilineage (mesodermal and decidual) differentiation potential. These findings support our view.…”

supporting

confidence: 66%

Mutation and methylation profiles of ectopic and eutopic endometrial tissues

Antero

Zhang

et al. 2021

The Journal of Pathology

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Adenomyosis and peritoneal endometriosis are common gynecologic lesions; they are characterized by aberrant locations of normal-appearing endometrium in myometrium and peritoneal surface, respectively. Both ectopic lesions are speculated to originate from uterine eutopic endometrium, which is composed of epithelium and stroma, but how these two different tissue types co-evolve in ectopic locations remains unclear. Here, we analyzed exome-wide mutations and global methylation in microdissected epithelium and stroma separately in paired adenomyosis, peritoneal endometriosis, and endometrium to investigate their relationship. Analyses of somatic mutations and their allele frequencies indicate monoclonal development not only in epithelium but also in the stroma of adenomyosis and peritoneal endometriosis. Our preliminary phylogenetic study suggests a plausible clonal derivation in epithelium and stroma of both ectopic and eutopic endometrium from the same founder epithelium-stroma progenitor cells. While a patient-specific methylation landscape is evident, adenomyosis epithelium and stroma can be distinguished from normal-appearing eutopic endometrium epigenetically. In summary, endometrial stroma, like its epithelial counterpart, could be clonal and both ectopic and eutopic endometrium following divergent evolutionary trajectories. Our data also warrant future investigations into the role of endometrial stroma in the pathobiology of endometriumrelated disorders.

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supporting

confidence: 66%

Mutation and methylation profiles of ectopic and eutopic endometrial tissues

Antero

Zhang

et al. 2021

The Journal of Pathology

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“…This suggests that the ‘menses-like’ material used to inoculate recipient mice in the DO and DI models may not contain the cell types required to establish chronic or progressive endometriosis. The cellular origins of endometriosis have yet to be fully elucidated ( Filby et al, 2020 ). However, it has been postulated that endometrial stem/progenitor cells are the cells of origin of endometriosis lesions ( Gargett, 2007 ; Cousins et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Bioluminescent imaging in induced mouse models of endometriosis reveals differences in four model variations

Dorning

Dhami

Panir

et al. 2021

Disease Models &Amp; Mechanisms

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Our understanding of the etiology and pathophysiology of endometriosis remains limited. Disease modelling in the field is problematic as many versions of induced mouse models of endometriosis exist. We integrated bioluminescent imaging of ‘lesions’ generated using luciferase-expressing donor mice. We compared longitudinal bioluminescence and histology of lesions, sensory behavior of mice with induced endometriosis and the impact of the GnRH antagonist Cetrorelix on lesion regression and sensory behavior. Four models of endometriosis were tested. We found that the nature of the donor uterine material was a key determinant of how chronic the lesions were as well as their cellular composition. The severity of pain-like behavior also varied across models. Whilst Cetrorelix significantly reduced lesion bioluminescence in all models, it had varying impacts on pain-like behavior. Collectively, our results demonstrate key differences in the progression of the ‘disease’ across different mouse models of endometriosis. We propose that validation and testing in multiple models, each of which may be representative of the different subtypes / heterogeneity observed in women should become a standard approach to discovery science in the field of endometriosis.

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“…Whilst the number of endometrial cells in the peritoneal fluid does not differ, the cell types contained in the shed tissue may have an important role. Indeed, it has been hypothesized that endometrial epithelial stem/progenitor cells are shed in menstrual fluid which gain access to the peritoneal cavity by retrograde menstruation where they initiate lesions via their clonogenic activity (Gargett, 2007b;Gargett et al, 2016;Cousins et al, 2018a;Filby et al, 2020). Women with endometriosis have more SSEA-1 + SOX9 + epithelial cells in their functionalis compared to normal women.…”

Section: Role Of Stem/progenitor Cells In Endometrial Pathologies-endometriosis and Endometrial Cancermentioning

confidence: 99%

The Elusive Endometrial Epithelial Stem/Progenitor Cells

Cousins

Pandoy

Jin

et al. 2021

Front. Cell Dev. Biol.

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The human endometrium undergoes approximately 450 cycles of proliferation, differentiation, shedding and regeneration over a woman’s reproductive lifetime. The regenerative capacity of the endometrium is attributed to stem/progenitor cells residing in the basalis layer of the tissue. Mesenchymal stem cells have been extensively studied in the endometrium, whereas endometrial epithelial stem/progenitor cells have remained more elusive. This review details the discovery of human and mouse endometrial epithelial stem/progenitor cells. It highlights recent significant developments identifying putative markers of these epithelial stem/progenitor cells that reveal their in vivo identity, location in both human and mouse endometrium, raising common but also different viewpoints. The review also outlines the techniques used to identify epithelial stem/progenitor cells, specifically in vitro functional assays and in vivo lineage tracing. We will also discuss their known interactions and hierarchy and known roles in endometrial dynamics across the menstrual or estrous cycle including re-epithelialization at menses and regeneration of the tissue during the proliferative phase. We also detail their potential role in endometrial proliferative disorders such as endometriosis.

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Cellular Origins of Endometriosis: Towards Novel Diagnostics and Therapeutics

Cited by 25 publications

References 129 publications

Mutation and methylation profiles of ectopic and eutopic endometrial tissues

Mutation and methylation profiles of ectopic and eutopic endometrial tissues

Bioluminescent imaging in induced mouse models of endometriosis reveals differences in four model variations

The Elusive Endometrial Epithelial Stem/Progenitor Cells

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